This analysis included 792 women and 228 live birth singletons with the following outcomes: 45.1% clinical pregnancy rate, 36.4% live birth rate. There were 324 patients who were estrogen administered orally and vaginally (OVE group), and 468 patients who were estrogen administered orally only (OE group). Baseline demographics and characteristics were compared between patients with different estrogen regimen (Table 1). Among the 792 women, it did not reveal any significant difference for maternal age, BMI, whether there was at least one good quality embryo transferred, progesterone route, E2 level at 14th day after transfer and P level at endometrium transform day between two groups. There were more patients with estradiol treatment days over 21 days in OVE group than in OE group. Serum E2 level at endometrium transform day from OVE group was significantly higher than those from OE group. Endometrium thickness at transform day was smaller in OVE group than OE group, as the same result for the endometrium thickness at HCG day in controlled ovarian stimulation (COS). No significant difference of live birth rate (Crude OR 1.229, 95CI% 0.917, 1.649) and clinical pregnancy rate (Crude OR 1.260, 95%CI 0.948, 1.675) was found between OVE and OE group (Table 2). Controlling for maternal age, BMI, whether estradiol duration was longer than 21 days, whether there was at least one good quality embryo transferred, the route of progesterone administration, endometrium thickness at endometrium transform day, estradiol administered regimen did not modify the odds of achieving live birth (Adjusted OR 1.327, 95%CI 0.982, 1.794, p=0.066) or clinical pregnancy (Adjusted OR 1.278, 95%CI 0.937, 1.743, p=0.121) (Table 2). Endometrium thickness at endometrium transform day positively increased the clinical pregnancy (Adjusted 1.184, 95%CI 1.026,1.365, p=0.021) with no impact on live birth rate (Adjusted OR 1.119, 95%CI 0.968, 1.295, p=0.130) (Supplementary Figure 1&2). Maternal age and at least one good quality embryo transferred were the independent factors that increased the live birth rate and clinical pregnancy rate (Supplementary Figure 1&2).
To further explore the estrogen regimen impact on birthweight and gestational age, a cohort of 228 live birth singletons from 792 patients was further investigated. The singletons were divided in two groups which were OVE group, and OE group. Baseline demographic and cycle characteristics were presented in Table 3. Comparison between the two groups did not reveal any significant difference for maternal age, BMI, whether there was at least one good quality embryo transferred and progesterone route. OVE group from 228 singletons cohort had more percentage of patients with longer days of estradiol treatment, thinner endometrium before FET and higher serum E2 level at endometrium transform day than OE group, as the same result with the 792 cohort (Table 3).
Neonatal outcomes stratified by the regimen of estradiol administered were also presented in Table 3. Preterm delivery rate, mean birthweight and Z-scores were not different across two groups (Table 3). Given that gestational age at delivery is an important determinant of newborn birthweight, a subgroup analysis was conducted stratified by term delivery. The analysis of gestational age between 32 to 36 weeks was not performed because the number in this category was too small. As shown in Table 3, Newborn gender, mean birthweight, LGA rate and SGA rate for term singletons were not different across the two groups.
In multivariate analyses (Table 4), the risk of preterm delivery (Adjusted OR 0.969, 95%CI 0.292, 3.214) and the risk of LGA (Adjusted OR 1.165, 95%CI 0.545, 2.490), SGA in term delivery (Adjusted OR 0.569, 95%CI 0.096, 3.369) were not significantly different between two groups after adjusting for maternal age, BMI, transfer with at least one good quality embryo, whether estrogen administration more than 21 days, endometrium thickness at endometrium transform day, progesterone route and newborn gender. The multivariate analysis of LGA and SGA for gestational age between 32 to 36 weeks was not performed because the number in this category was too small. After correction for a number of potential confounders, the route of estradiol administered was not correlated with neonatal birthweight (β=-30.962, SE=68.723, p=0.653) (Table 5).