Thick endometrium is associated with hypertensive disorders of pregnancy in programmed frozen-thawed embryo transfers: a retrospective analysis of 2,275 singleton deliveries

Objective To investigate whether endometrial thickness (EMT) acts as a contributing factor to adverse perinatal outcomes in programmed frozen-thawed embryo transfer (FET) cycles. Design Retrospective cohort study. Setting University-based reproductive medical center. Subject The study included singleton live births resulting from programmed FET cycles that took place between January 2017 and April 2022 (N=2275 cycles). Exposure The EMT measurement conducted on the day of progesterone initiation was utilized. Programmed FET cycles with EMT less than 7 mm were excluded from consideration. All included subjects were divided into four groups based on the 10th, 50th, and 90th percentiles of EMT: group Ⅰ (EMT ≤8 mm, n = 193), group Ⅱ (EMT = 8.1-10 mm, n = 1261), group Ⅲ (EMT = 10.1-12 mm, n = 615), and group Ⅳ (EMT ≥12 mm, n = 206). After adjusting for patient demographics and FET parameters, logistic regression analysis and restricted cubic spline (RCS) were used to investigate the relationship between EMT and perinatal outcomes. The group Ⅱ (EMT = 8.1-10 mm) served as reference. Main outcome measure(s) The primary outcome measure was the hypertensive disorders of pregnancy (HDP). Secondary outcomes included gestational diabetes mellitus, caesarean delivery, placenta previa, premature rupture of membrane, birthweight, preterm birth, low birthweight, macrosomia, small for gestational age, large for gestational age and neonatal morbidity. Results(s) The incidence of HDP was substantially elevated in group Ⅳ when compared to the other groups (5.7% vs. 4.1% vs. 5.7% vs. 9.7% for groups Ⅰ-Ⅳ, respectively). Additionally, group I displayed a higher incidence of caesarean deliveries, whereas both group I and group IV exhibited an elevated prevalence of placenta previa. After adjusting for confounding factors, patients in group IV exhibited a significantly increased risk of HDP (adjusted odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.13-3.67) as compared to patients in the reference group. In addition, the RCS model revealed a nonlinear association between EMT and the odds of HDP on continuous scales. In comparison to women with an EMT of 9.5 mm, there was no significant change in the risk of HDP in women with EMT between 7 and 11 mm, as indicated by adjusted ORs of 1.37 (95% CI 0.41-4.52), 1.34 (95% CI 0.73-2.47), 1.13 (95% CI 0.79-1.62), 1.04 (95% CI 0.87-1.25), and 1.46 (95% CI 0.81-2.65), respectively. However, the risk of HDP was significantly higher in women with EMT ranging from 12 to 15 mm, with adjusted ORs of 1.86 (95% CI 1.03-3.35), 2.33 (95% CI 1.32-4.12), 2.92 (95% CI 1.52-5.64), and 3.62 (95% CI 1.63-8.04), respectively. Conclusion(s) This study demonstrated a noteworthy association between EMT and adverse perinatal outcomes during the programmed FET cycles. Specifically, a thick endometrium (EMT >12 mm) was independently associated with an increased risk of developing HDP, while the optimal EMT for reducing risk of HDP was at around 9-10 mm. To investigate whether endometrial thickness (EMT) acts as a contributing factor to adverse perinatal outcomes in programmed frozen-thawed embryo transfer (FET) cycles. Retrospective cohort study. University-based reproductive medical center. The study included singleton live births resulting from programmed FET cycles that took place between January 2017 and April 2022 (N=2275 cycles). The EMT measurement conducted on the day of progesterone initiation was utilized. Programmed FET cycles with EMT less than 7 mm were excluded from consideration. All included subjects were divided into four groups based on the 10th, 50th, and 90th percentiles of EMT: group Ⅰ (EMT ≤8 mm, n = 193), group Ⅱ (EMT = 8.1-10 mm, n = 1261), group Ⅲ (EMT = 10.1-12 mm, n = 615), and group Ⅳ (EMT ≥12 mm, n = 206). After adjusting for patient demographics and FET parameters, logistic regression analysis and restricted cubic spline (RCS) were used to investigate the relationship between EMT and perinatal outcomes. The group Ⅱ (EMT = 8.1-10 mm) served as reference. The primary outcome measure was the hypertensive disorders of pregnancy (HDP). Secondary outcomes included gestational diabetes mellitus, caesarean delivery, placenta previa, premature rupture of membrane, birthweight, preterm birth, low birthweight, macrosomia, small for gestational age, large for gestational age and neonatal morbidity. The incidence of HDP was substantially elevated in group Ⅳ when compared to the other groups (5.7% vs. 4.1% vs. 5.7% vs. 9.7% for groups Ⅰ-Ⅳ, respectively). Additionally, group I displayed a higher incidence of caesarean deliveries, whereas both group I and group IV exhibited an elevated prevalence of placenta previa. After adjusting for confounding factors, patients in group IV exhibited a significantly increased risk of HDP (adjusted odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.13-3.67) as compared to patients in the reference group. In addition, the RCS model revealed a nonlinear association between EMT and the odds of HDP on continuous scales. In comparison to women with an EMT of 9.5 mm, there was no significant change in the risk of HDP in women with EMT between 7 and 11 mm, as indicated by adjusted ORs of 1.37 (95% CI 0.41-4.52), 1.34 (95% CI 0.73-2.47), 1.13 (95% CI 0.79-1.62), 1.04 (95% CI 0.87-1.25), and 1.46 (95% CI 0.81-2.65), respectively. However, the risk of HDP was significantly higher in women with EMT ranging from 12 to 15 mm, with adjusted ORs of 1.86 (95% CI 1.03-3.35), 2.33 (95% CI 1.32-4.12), 2.92 (95% CI 1.52-5.64), and 3.62 (95% CI 1.63-8.04), respectively. This study demonstrated a noteworthy association between EMT and adverse perinatal outcomes during the programmed FET cycles. Specifically, a thick endometrium (EMT >12 mm) was independently associated with an increased risk of developing HDP, while the optimal EMT for reducing risk of HDP was at around 9-10 mm.