Impact of different endometrial preparation protocols on pregnancy outcomes in frozen-thawed embryo transfer cycles among patients ≤35 years with a history of intrauterine adhesion separation surgery: a retrospective cohort study

Objective To investigate the impact of three endometrial preparation protocols-hormone replacement therapy (HRT), natural cycle (NC), and down-regulation HRT-on pregnancy outcomes in frozen embryo transfer (FET) cycles among patients with a history of intrauterine adhesion (IUA) separation surgery. Method A retrospective cohort study was conducted to analyze the data from FET cycles at reproductive medicine center from January 2017 to December 2023. The patients with a history of intrauterine adhesion separation surgery were classified into three groups: the HRT group (n=285), the NC group (n=200), and the down-regulation HRT group (n=104). Baseline characteristics and reproductive outcomes were compared between the groups. Chi-square tests were used for univariate analysis, and multivariate logistic regression analysis was conducted to adjust for confounding factors. Results There were statistically significant differences among the three groups in terms of general charateristics (all P<0.05). The clinical pregnancy rates for the HRT group, NC group, and down-regulation-HRT group were 30.88% (88/285), 47.50% (95/200), and 40.38% (42/104) respectively. The biochemical pregnancy rates were 35.09% (100/285), 50.50% (101/200), and 45.19% (57/104) respectively. The early miscarriage rates were 21.59% (19/88), 13.68% (13/95), and 21.43% (9/42) respectively, and the live birth rates were 22.81% (65/285), 36.50% (73/200), and 30.77% (32/104) respectively. There were statistically significant differences in clinical pregnancy rate, biochemical pregnancy rate and live birth rate among the groups. Following adjusting for confounding factors, the NC group exhibited significantly higher clinical pregnancy rate (aOR=1.627, 95% CI: 1.079-2.453, P = 0.02) and biochemical pregnancy rate (aOR=1.532, 95% CI: 1.020~2.301, P = 0.04) relative to the HRT group. There were no statistically significant differences in live birth rate, and early miscarriage rate (all P>0.05). Similarly, there were no statistically significant differences in clinical pregnancy rate, biochemical pregnancy rate, live birth rate, and early miscarriage rate between the down-regulation-HRT group and the HRT group (all P>0.05). Conclusion For patients undergoing FET cycle with a history of IUA separation surgery, the live birth rate is similar between three groups. However, the natural cycle endometrial preparation protocol yielded higher clinical and biochemical pregnancy rates than the HRT protocol, suggesting its potential clinical advantage for these patients.