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Updated: Jun 30, 2026
Establishment of an Embryo Implantation Model In Vitro
Published on: June 21, 2024
Effect of Low-Dose Estradiol on the Clinical Pregnancy Rate of the Hormone Replacement Frozen-Thawed Embryo Transfer
Chenyang Huang1,2,3, Jingyu Liu1,2,3, Yingchun Zhu1,2,3
1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, People's Republic of China.
Background:
The hormone replacement therapy (HRT) is widely used for endometrial preparation in frozen-thawed embryo transfer (FET), but non-physiological estrogen levels may increase pregnancy complications. This study examined whether reducing the estrogen dose maintains clinical pregnancy rates.
Methods:
This retrospective cohort study included patients undergoing HRT-FET with single blastocyst transfer (Jan 2022 - Jun 2025). Patients were divided into a high-dose group (Group A, starting dose 6 mg/day, n = 1955) and a low-dose group (Group B, starting dose 2 mg/day, maximum increment 2 mg/day, n = 202). The primary outcome was clinical pregnancy rate. Due to the bias in clinical decision, the high estradiol dose protocol is typically prioritized, resulting in a significant difference in sample sizes between the two groups. Univariate analysis, multivariate logistic regression, and propensity score matching were used to control for confounders.
Results:
Before adjustment, the clinical pregnancy rate was significantly higher in the low-dose group (79.21%) than in the high-dose group (69.57%). However, baseline differences existed in female age and ovarian reserve parameters between groups. After multivariate adjustment, the increase in clinical pregnancy rates in the low-dose group was not significant (aOR = 1.422, 95% CI: 0.983-2.055, P = 0.061). Analysis after propensity score matching also showed no significant differences in clinical pregnancy (76.3% vs. 78.6%, P = 0.599) or early miscarriage rates (10.2% vs. 13.9%, P = 0.251).
Conclusion:
The finding that reducing the starting dose of exogenous estrogen in HRT-FET cycles did not appear to compromise clinical pregnancy outcomes following single blastocyst transfer suggests that an individualized lower-dose estrogen strategy may be feasible, particularly for younger women or those with normal ovarian reserve. However, these results are preliminary, and prospective clinical trials are needed to confirm whether such an approach can maintain efficacy while potentially reducing risks associated with high estrogen exposure.
